Neurodevelopment of children born very preterm and free of severe disabilities: the Nord-Pas de Calais Epipage cohort study.
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ABSTRACT: Aim
To describe the development of very preterm children free of cerebral palsy or severe sensory impairment in the domains of gross and fine motor functions, language and sociability at a corrected age of 2 years; to identify factors associated with performances in each domain.Methods
A total of 347 children born in 1997 before 33 weeks of gestation, part of the EPIPAGE population-based cohort study, had their psychomotor development assessed with the Brunet-Lezine scale.Results
The study population had a mean gestational age of 30.1 +/- 2.0 weeks. Lower developmental quotients (DQ) were observed in the study group compared to the reference sample (96 +/- 13 vs 104 +/- 8, p < 0.01). Fine motor function, language and sociability were all affected with a p value <0.01. Multivariate analysis showed that duration of intubation and parents' educational and occupational levels were the only variables significantly related to each developmental domain (p < 0.01).Conclusions
Children very preterm and free of severe disabilities had mild delays in multiple areas of development. The mechanisms by which neonatal factors played a role need further investigation. However socioeconomic status had a great impact on development and our results underline the need for improved support of socioeconomically disadvantaged parents after a preterm birth.
SUBMITTER: Charkaluk ML
PROVIDER: S-EPMC4823384 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE: To investigate the association of motor and cognitive/learning deficiencies and overall disabilities in very preterm (VPT) children and their relations to gestational age (GA) and brain lesions. DESIGN SETTING AND PARTICIPANTS: EPIPAGE is a longitudinal population-based cohort study of children born before 33 weeks' gestation (WG) in 9 French regions in 1997-1998. Cumulating data from all follow up stages, neurodevelopmental outcomes were available for 90% of the 2480 VPT survivors at 8 years. Main outcomes were association of motor and cognitive deficiencies and existence of at least one deficiency (motor, cognitive, behavioral/psychiatric, epileptic, visual, and/or hearing deficiencies) in three GA groups (24-26, 27-28, and 29-32WG) and four groups of brain lesions (none, minor, moderate, or severe). RESULTS: VPT had high rates of motor (14%) and cognitive (31%) deficiencies. Only 6% had an isolated motor deficiency, 23% an isolated cognitive one and 8% both types. This rate reached 20% among extremely preterm. Psychiatric disorders and epilepsy were observed in 6% and 2% of children, respectively. The risks of at least one severe or moderate deficiency were 11 and 29%. These risks increased as GA decreased; only 36% of children born extremely preterm had no reported deficiency. Among children with major white matter injury (WMI), deficiency rates reached 71% at 24-26WG, 88% at 27-28WG, and 80% at 29-32WG; more than 40% had associated motor and cognitive deficiencies. By contrast, isolated cognitive deficiency was the most frequent problem among children without major lesions. CONCLUSIONS: In VPT, the lower the GA, the higher the neurodisability rate. Cerebral palsy is common. Impaired cognitive development is more frequent. Its occurrence in case without WMI or early motor disorders makes long-term follow up necessary. The strong association between motor impairments, when they exist, and later cognitive dysfunction supports the hypothesis of a common origin of these difficulties.
| S-EPMC3642195 | biostudies-other
Project description:ObjectivesTo describe neurodevelopment at age 5 among children born preterm.DesignPopulation based cohort study, EPIPAGE-2.SettingFrance, 2011.Participants4441 children aged 5½ born at 24-26, 27-31, and 32-34 weeks MAIN OUTCOME MEASURES: Severe/moderate neurodevelopmental disabilities, defined as severe/moderate cerebral palsy (Gross Motor Function Classification System (GMFCS) ≥2), or unilateral or bilateral blindness or deafness, or full scale intelligence quotient less than minus two standard deviations (Wechsler Preschool and Primary Scale of Intelligence, 4th edition). Mild neurodevelopmental disabilities, defined as mild cerebral palsy (GMFCS-1), or visual disability ≥3.2/10 and <5/10, or hearing loss <40 dB, or full scale intelligence quotient (minus two to minus one standard deviation) or developmental coordination disorders (Movement Assessment Battery for Children, 2nd edition, total score less than or equal to the fifth centile), or behavioural difficulties (strengths and difficulties questionnaire, total score greater than or equal to the 90th centile), school assistance (mainstream class with support or special school), complex developmental interventions, and parents' concerns about development. The distributions of the scores in contemporary term born children were used as reference. Results are given after multiple imputation as percentages of outcome measures with exact binomial 95% confidence intervals.ResultsAmong 4441 participants, 3083 (69.4%) children were assessed. Rates of severe/moderate neurodevelopmental disabilities were 28% (95% confidence interval 23.4% to 32.2%), 19% (16.8% to 20.7%), and 12% (9.2% to 14.0%) and of mild disabilities were 38.5% (33.7% to 43.4%), 36% (33.4% to 38.1%), and 34% (30.2% to 37.4%) at 24-26, 27-31, and 32-34 weeks, respectively. Assistance at school was used by 27% (22.9% to 31.7%), 14% (12.1% to 15.9%), and 7% (4.4% to 9.0%) of children at 24-26, 27-31, and 32-34 weeks, respectively. About half of the children born at 24-26 weeks (52% (46.4% to 57.3%)) received at least one developmental intervention which decreased to 26% (21.8% to 29.4%) for those born at 32-34 weeks. Behaviour was the concern most commonly reported by parents. Rates of neurodevelopment disabilities increased as gestational age decreased and were higher in families with low socioeconomic status.ConclusionsIn this large cohort of children born preterm, rates of severe/moderate neurodevelopmental disabilities remained high in each gestational age group. Proportions of children receiving school assistance or complex developmental interventions might have a significant impact on educational and health organisations. Parental concerns about behaviour warrant attention.
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Project description:BackgroundThe pathogenesis of late-onset sepsis (LOS) in preterm infants is poorly understood and knowledge about risk factors, especially prenatal risk factors, is limited. This study aimed to assess the association between the cause of preterm birth and LOS in very preterm infants.Methods2052 very preterm singletons from a national population-based cohort study alive at 72 h of life were included. Survival without LOS was compared by cause of preterm birth using survival analysis and Cox regression models.Results437 (20.1%) had at least one episode of LOS. The frequency of LOS varied by cause of preterm birth: 17.1% for infants born after preterm labor, 17.9% after preterm premature rupture of membranes, 20.3% after a placental abruption, 20.3% after isolated hypertensive disorders, 27.5% after hypertensive disorders with fetal growth restriction (FGR), and 29.4% after isolated FGR. In multivariate analysis, when compared to infants born after preterm labor, the risk remained higher for infants born after hypertensive disorders (hazard ratio HR = 1.7, 95% CI = 1.2-2.5), hypertensive disorders with FGR (HR = 2.6, 95% CI = 1.9-3.6) and isolated FGR (HR = 2.9, 95% CI = 1.9-4.4).ConclusionVery preterm infants born after hypertensive disorders or born after FGR had an increased risk of LOS compared to those born after preterm labor.ImpactLate-onset sepsis risk differs according to the cause of preterm birth. Compared with those born after preterm labor, infants born very preterm because of hypertensive disorders of pregnancy and/or fetal growth restriction display an increased risk for late-onset sepsis. Antenatal factors, in particular the full spectrum of causes leading to preterm birth, should be taken into consideration to better prevent and manage neonatal infectious morbidity and inform the parents.
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Project description:Supplementation of breast milk is difficult once infants suckle the breast and is often discontinued at end of hospitalisation and after discharge. Thus, breastfed preterm infants are exposed to an increased risk of nutritional deficit with a possible consequence on neurodevelopmental outcome.To assess the relationship between breast feeding at time of discharge, weight gain during hospitalisation and neurodevelopmental outcome.Observational cohort study.Two large, independent population-based cohorts of very preterm infants: the Loire Infant Follow-up Team (LIFT) and the EPIPAGE cohorts.2925 very preterm infants alive at discharge.Suboptimal neurodevelopmental outcome, defined as a score in the lower tercile, using Age and Stages Questionnaire at 2 years in LIFT and Kaufman Assessment Battery for Children Test at 5 years in EPIPAGE. Two propensity scores for breast feeding at discharge, one for each cohort, were used to reduce bias.Breast feeding at time of discharge concerned only 278/1733 (16%) infants in LIFT and 409/2163 (19%) infants in EPIPAGE cohort. Breast feeding is significantly associated with an increased risk of losing one weight Z-score during hospitalisation (LIFT: n=1463, adjusted odd ratio (aOR)=2.51 (95% CI 1.87 to 3.36); EPIPAGE: n=1417, aOR=1.55 (95% CI 1.14 to 2.12)) and with a decreased risk for a suboptimal neurodevelopmental assessment (LIFT: n=1463, aOR=0.63 (95% CI 0.45 to 0.87); EPIPAGE: n=1441, aOR=0.65 (95% CI 0.47 to 0.89) and an increased chance of having a head circumference Z-score higher than 0.5 at 2 years in LIFT cohort (n=1276, aOR=1.43 (95% CI 1.02 to 2.02)) and at 5 years in EPIPAGE cohort (n=1412, aOR=1.47 (95% CI 1.10 to 1.95)).The observed better neurodevelopment in spite of suboptimal initial weight gain could be termed the 'apparent breastfeeding paradox' in very preterm infants. Regardless of the mechanisms involved, the current data provide encouragement for the use of breast feeding in preterm infants.
| S-EPMC3323805 | biostudies-other
Project description:Language deficits are reported in preterm born children across development. Recent neuroimaging studies have found functional alterations in large-scale brain networks underlying these language deficits, but the early childhood development of the language network has not been investigated. Here, we compared intrinsic language network connectivity in 4-year-old children born VPT and term-born controls, using defined language regions (Broca's area, Wernicke's areas, and their homologues in the right hemisphere). Resting-state functional magnetic resonance imaging (fMRI) was obtained, and the group differences in whole-brain connectivity were examined from each seed as well as correlations with language outcomes. We found significantly decreased functional connectivity in almost all language regions in children born VPT compared to their term controls. Notably, Broca's area homologue in the right hemisphere emerged as a functional hub of decreased connectivity in VPT group, specifically to bilateral inferior frontal and supramarginal gyri; connectivity strength between Broca's area homologue with the right supramarginal and the left inferior frontal gyri was associated with better language outcomes at 4 years of age. Wernicke's area and its homologue also showed decreased inter-hemispheric connections to bilateral supramarginal gyri in the VPT group. Decreased intra- and inter-hemispheric connectivity among primary language regions suggests immature and altered function in the language network in children born VPT.
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Project description:ObjectiveTo determine whether there is an association between severe intraventricular hemorrhage and early extubation in preterm infants born before 29 weeks of gestational age and intubated at birth.MethodsThis study included 1587 preterm infants from a nationwide French population cohort (EPIPAGE-2). Secondary data on intubated preterm infants were analyzed. After gestational age and propensity score matching (1:1) we built two comparable groups: an early extubation group and a delayed extubation group. Each neonate in one group was paired with a neonate in the other group having the same propensity score and gestational age. Early extubation was defined as extubation within 48 hours of life. Severe intraventricular hemorrhages were defined as grade III or IV hemorrhages according to the Papile classification.ResultsAfter matching, there were 398 neonates in each group. Using a generalized estimating equation model, we found that intraventricular hemorrhage was not associated with early extubation (adjusted OR 0.9, 95%CI 0.6-1.4). This result was supported by sensitivity analyses.ConclusionThe practice of early extubation was not associated with an increased proportion of intraventricular hemorrhages. To complete these results, the long-term neurologic outcomes of these infants need to be assessed.
| S-EPMC6448867 | biostudies-literature
Project description:Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing.
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Project description:Many children born very preterm (?32 weeks) experience significant cognitive difficulties, but the biological basis of such problems has not yet been determined. Functional MRI studies have implicated altered functional connectivity; however, little is known regarding the spatiotemporal organization of brain networks in this population. We provide the first examination of resting-state neuromagnetic connectivity mapped in brain space in school age children born very preterm. Thirty-four subjects (age range 7-12 years old), consisting of 17 very preterm-born children and 17 full-term born children were included. Very preterm-born children exhibited global decreases in inter-regional synchrony in all analysed frequency ranges, from theta (4-7 Hz) to high gamma (80-150 Hz; p < 0.01, corrected). These reductions were expressed in spatially and frequency specific brain networks (p < 0.0005, corrected). Our results demonstrate that mapping connectivity with high spatiotemporal resolution offers new insights into altered organization of neurophysiological networks which may contribute to the cognitive difficulties in this vulnerable population.
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Project description:Cortical resting state networks have been consistently identified in infants using resting state-functional connectivity magnetic resonance imaging (rs-fMRI). Comparable studies in adults have demonstrated cerebellar components of well-established cerebral networks. However, there has been limited investigation of early cerebellar functional connectivity. We acquired non-sedated rs-fMRI data in the first week of life in 57 healthy, term-born infants and at term-equivalent postmenstrual age in 20 very preterm infants (mean birth gestational age 27 ± 2 weeks) without significant cerebral or cerebellar injury. Seed correlation analyses were performed using regions of interests spanning the cortical and subcortical gray matter and cerebellum. Parallel analyses were performed using rs-fMRI data acquired in 100 healthy adults. Our results demonstrate that cortico-cerebellar functional connectivity is well-established by term. Intra- and cortico-cerebellar functional connectivity were largely similar in infants and adults. However, infants showed more functional connectivity structure within the cerebellum, including stronger homotopic correlations and more robust anterior-posterior anticorrelations. Prematurity was associated with reduced correlation magnitudes, but no alterations in intra- and cortico-cerebellar functional connectivity topography. These results add to the growing evidence that the cerebellum plays an important role in shaping early brain development during infancy.
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